TW474828B - A method and apparatus for use in the UV-irradiation of a biological fluid - Google Patents

Abstract

The present invention relates to a method and apparatus for effective inactivation of micro-organisms in fluids with relatively high absorbance so as to limit damage. The apparatus has a large diameter passage 2 flow-through UV radiation system with a static mixer system 11 providing an intensive fluid flow mixing within an irradiation area in which the fluid flow is controlled to provide a flow rate not less than a minimum flow rate corresponding to a maximum fluid residence time within said irradiation area required for efficient mixing, and a maximum flow rate providing a minimum residence time for effective inactivation.

Description

474828 Printed by A7 B7, Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the Invention (/) The present invention relates to a method and device for irradiating biological liquids with high optical density, such as those used in the food industry, including dairy industry, Steam storage and brewing industry, as well as water treatment industry including sewage engineering and purification industry, especially deactivating microorganisms and lymphocytes and the like, including viruses, molds, yeasts and other blood and Blood-derived products, as well as many other body fluids, such as milk from transgenic animals' and organisms in artificial fluids that are used to replace any such body fluids or substitutes for them. Deactivation of lymphocytes in biological fluids is conventionally achieved by administering immunosuppressive drugs to patients. However, this step contains serious risks for patients because of the many adverse and often severe side effects of these drugs. 'Although many different steps for the extracorporeal treatment of blood have been previously proposed, these steps do not affect the lymphocyte population. Produces complete inactivation, and / or is operated with relatively inconvenient, expensive and / or impractical devices. In the case of infection with microorganisms such as bacteria and viruses, many treatment methods have been proposed, including Prolonged incubation at temperature and microwave irradiation 'these processing methods are usually quite slow (hours to even days)' and generally require quite expensive equipment and safety precautions followed by operators with strict equipment. It has also been found that a combination of ultraviolet irradiation and the use of chemical additives such as photosensitizers such as furocoumarins can be used to increase the effectiveness of the irradiation step (represented by 10 gl. Killing radon). A typical example of this type of method can be found in WO09 4/2 8 1 2 0 (MARGOLIS- This paper size applies the Chinese National Standard (CNS) A4 regulations; (21〇x 297 feet) M.— I n. Nnnnn a δ, t I nna ^ inn II nn κ I n 1 I nnn! (Please read the notes on the back before filling this page) 474828 A7 B7___ V. Description of the invention (2) NUNNO) and W095 / 32732 (PARKKINEN). (Please read the precautions on the back before filling out this page) It has been proposed to add photo-sensitive chemicals such as furanosuccinidin to biological liquids so as to achieve effective energy transfer from ultraviolet sources to target microorganisms, thereby killing or enabling microorganisms Inactivation, untranslated excessive doses of radiation that may be harmful to components in biological fluids. In more detailed microorganisms, viruses and other infectious agents of biological fluids can be photodynamically inactivated by adding photosensitizers to the liquid, and then can be irradiated. The photosensitizer can transfer the energy obtained from the irradiation to the micro-organisms by, for example, an electron transfer reaction. The second mode of deactivation by photo-sensitive compounds (most often in the presence of nucleic acids) is that the photo-sensitive compounds react with nucleic acid residues under irradiation. It is generally guanopurine in DNA. This reaction will cause nucleic acid residues. Radical deactivation 'and thus deactivate the microorganism. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. Although the addition of chemicals to biological fluids has the disadvantage that the chemicals and / or their decomposition products still exist in biological fluids after irradiation, generally speaking, 'this is due to chemicals and / or These decomposition products are the source of biological fluid infections and are therefore undesirable. In addition, the chemicals themselves can be quite expensive and require additional steps to add them to the biological fluid, which can be time consuming, and therefore costly in terms of labor and manpower, and also bring potential sources of error for the effective handling of biological fluids. In order to remove or deactivate the chemicals and / or their decomposition products', it is necessary to provide one or more additional steps in the processing method and its apparatus for processing biological liquids, which obviously has a cost problem. Exposure of biological fluids to ultraviolet light can cause damage to many components in biological fluids, such as enzymes and other functional proteins. Therefore, if 4 paper sizes are applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 494828 printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 5. The invention description (3) is to avoid the components in the liquid Damage, the source of UV light should not be too strong and the liquid should not be exposed to UV light for too long. To ensure that substantially all of the liquid receives a sufficient dose of irradiation, it has been found that vigorous mixing of the liquid to be treated during the irradiation increases the efficiency of the irradiation method. The device equipped with an extremely effective mixer is described in the applicant's patent GB2,200,00B, and the device of GB2,200,002B is described with a particularly stable flow mixing device, which is The device is used to repeatedly separate and mix biological liquids during irradiation. GB 2, 2 0 0, 0 2 〇 The main device of B has multiple narrow-diameter (= 2 mm) channels (see 'Lines 16 to 19' on page 5) , Use this stove to make biological fluid flow through the channel. These narrow channels ensure that biological fluids receive a sufficient dose of ultraviolet radiation by irradiating the biological fluids close to the device's ultraviolet rays (i.e., at a distance of less than 1 mm) to the transparent walls. Biological fluids must be close to these walls because many biological fluids Ultraviolet radiation has a relatively high absorption, especially liquids with high 0 D 値, such as blood, and almost _ bright but liquids with relatively 0 D 値, for example, with 0 2 8 Q 2 24 · 5 Human blood albumin (HSA) generally has a plasma with 0j) 2 ~ 〇 値 of 50 to 60, and different immunogamma globulins (ig) which may have 0 D 2800 値 of 2000 or more. G), which means that it is difficult for the irradiation to completely penetrate the biological fluid. The intensity of ultraviolet radiation in a biological liquid at a specific point is proportional to the area inverse of the distance from the point to the source of ultraviolet radiation, because the biological fluid system passes through a narrow-diameter channel when using the device described in GB2,200,020B. A device such as the main device described in GB 2, 2 ^ 0, 0 2 〇 B, one of the limitations of which is due to the application of the Chinese National Standard (CNS) A4 specification (210 X 297 public love — 11 n) I n I 1 I In H ^ 1 ^ 1 Baal Βϋ I ta ^ lnntnnnn II nn, {Please read the notes on the back before filling out this page) 4 ^ 4828 Printed by A7 B7, Consumer Cooperatives, Intellectual Property Bureau, Ministry of Economic Affairs Description of the invention (β) Through such narrow-diameter channels, biological fluids will be damaged by heat from the source of irradiation, which heats the walls of the device and damages the main components of biological fluids, such as proteins, red blood cells, and others. Thermal damage is undesirable and is a limiting factor in the use of stronger sources of radiation and their proximity to the liquid to be treated. To reduce thermal damage, the irradiation chamber of the device may be cooled, for example, by air cooling, using a fan as described in Example 1 of GB 2,200,002. However, due to the relatively low flow rate (eg, 130 ml / min to 12,000 ml / min), the biological fluid is in contact with the wall of the device or is very close to it for a considerable period of time, which results in relatively high thermal damage. Dangerous. Another problem that arises in this field is to minimize thermal damage and damage from excessive irradiation 'to minimize processing time or residence time in the irradiated area. On the other hand, if the residence time is too short, a safe amount of virus inactivation or 10 g killing radon may not be achieved. However, inactivation on a commercial scale involves the treatment of relatively large volumes of precious and scarce substances such as albumin, IgG, plasma, and the like, which are hundreds or thousands of liters, and they are very expensive and waste precious and Rare materials are used to perform many different processing parameters and conditions that are quite large for each batch of material being processed. Therefore, there is an important need to provide a device that predicts 10 g kills of different liquid batches with different 0 d s 値, such as OD28 for plasma.値 Generally can be between 4 5 and 5 5 and below. It is an object of the present invention to provide a method and a device for treating biological fluids to kill or inactivate microorganisms and the like to avoid or reduce at least -------- order --------- Line 'Please read the back of the page first. Please write this page ℴ Order 74828 A7 B7 V. Description of the invention (r) • The above disadvantages are printed by the Ministry of Economic Affairs, the Ministry of Economic Affairs, J. Bureau, and Consumer Cooperatives. Surprisingly, it has been found that the effective killing or inactivation of microorganisms in OD 28Q 値 liquids with a relatively high absorbance, typically in the range of 1 to 200, can be effective in a circulation system to maximize inactivation To effectively control damage and limit damage. More specifically, we have found that the rate of inactivation of microorganisms-called 10 g killing pupae-can be effectively controlled to flow through a relatively large diameter channel by using a stable mixer system that is formed and installed This type of liquid in the ultraviolet irradiation system provides a strong liquid flow mixing in an irradiation area, wherein the liquid flow in the large diameter channel is irradiated with ultraviolet radiation with a wavelength of deactivation of the microorganisms, and the liquid flow rate is controlled To provide a flow rate that is not less than the minimum flow rate corresponding to the maximum liquid retention time in the irradiation area required for effective mixing, as shown below ... As predicted by the actual 10 g killing 値 and predicted by the relationship shown below The maintenance of a substantial close relationship between 10 g of killing plutonium is carried out by obtaining the increased residence time of the minimum flow rate mentioned above, or for the liquid flow to ^ 5 ◦ at least 1 0 0 Reynolds number, and to provide a (minimum) desired kill rate, by passing a liquid through the illuminated area with a (minimum) residence time in the illuminated area That residence time line is defined according to the following relationship: square g 1. A dead 値 = KX flux (fiux) x residence time x Z / 〇dx tube diameter where flux refers to the channel that contains the liquid flow in the irradiation area = the amount of external irradiation (near the channel wall), WmW cm_2 indicates that the 0D is the ultraviolet irradiation wavelength of the inactivated microorganism (normally 297 mm for the 5th scale) (please read the precautions on the back before filling this page) like β β > — n · ^^ 1 n 1 ^^ 1 It ^^ 1 HI ^^ 1 nnnnnnnn · n · it— imt in nn 474828 A7 B7 V. Description of the invention (6) is the optical density of the liquid in the range of 2 50 to 2 0 8 microns) K is a constant derived from experiments; tube diameter is the inner diameter of the container in the irradiation area, expressed in cms; and Z is a specific physical property that affects the liquid flowing through the ultraviolet irradiation channel. In more detail, Z = u (ρ / μ) / Rem where u is the liquid flow rate in centimeters per second, p is the liquid density in kg / m3, and μ is c c as Unit of liquid viscosity, Re is the Reynolds number of the liquid, this 値 is defined by the formula Re = du ρ / μ 'where d, u, p and μ have the same definitions as above, and m is stable for this A characteristic of the hybrid system, the actinide is determined experimentally. In the case of such a stable flow mixing system including a plurality of alternately rotating radial deviating half-turn helical screw members, which is further described below, m generally has a magnitude of 0.4. It will be appreciated that the above relation can be expressed in many different ways and / or can be simplified to a greater or lesser extent by maintaining a variable constant. So, for example, if the source of UV radiation (number of lamps used, arrangement, type of power 'separation', etc.) is kept constant, the change in irradiation flux will only follow the UV (transmission characteristics of the walls that define the channel) , The processed liquid flows through the channel, and for the wall material defining the channel, 値 T m can be transmitted relative to the irradiation instead of "flux") and a constant that can be inserted into the general constant K of the general relationship above It depends. By way of example, if the transmission property of silica glass with a specific wall thickness 1.0, the Tm 値 of plastic FEP (fluorinated ethylene propylene) with the same wall thickness is 0.8 8 This paper size applies the Chinese National Standard (CNS ) A4 size (210 x 297 mm) ------------% (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs

474828 A7 B7 V. Description of the invention (7) 3 By extracting the u component from Z and combining it with the residence time component tR, the above relationship may be expressed in the following form:

1 〇g 1 〇 Kill 値 = K · T m (p / »L 〇D · d · R e 04 where L is the total effective length of the irradiation area (that is, the actual length x the number of passes), and other symbols have as above In addition, it has been found that the above relationship can be simplified somewhat for liquids with a lower range of OD s 1 (generally between 1 and 50, especially between 1 and 30). Therefore, on the one hand, it has also been found that OD28Q 値, which has a relatively high absorption-generally in the range of 1 to 200, effectively kills or inactivates microorganisms and can effectively kill them in a circulation system with one kind. To effectively control the way of maximizing life and limiting damage. More specifically, we have found that the rate of microbial inactivation-called 10 g kills pupae-can be effectively controlled by the use of a stable mix of formation and installation Device to control the flow of such liquid in the ultraviolet irradiation system through a relatively large diameter channel to provide a violent liquid flow mixing in an irradiation area, wherein the liquid flow in the large diameter channel is removed by a microorganism. Active wavelength of ultraviolet Radiation to irradiate, and control the liquid flow rate to provide a minimum flow rate not less than the maximum liquid residence time in the irradiation area required for effective mixing, such as obtained by killing radon at 10 g and above the minimum flow rate The maintenance of a substantially linear relationship between the residence time of d is shown, and a (minimum) desired kill rate of 10 g is obtained through the flow of liquid through the illuminated area to provide (minimum) residence in the illuminated area. Time, its residence time is defined according to the following relationship: 9 This paper size applies to China National Elephant Standard (CNS) A4 specification (210 X 297 public love) -------------% ( (Please read the notes on the back before filling out this page)

Order --------- Line II Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 474828 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (?) Flux X residence time / 0D X tube diameter, where flux refers to the amount of ultraviolet radiation occurring on the channel containing the liquid flow in the irradiation area, expressed in m W cm-2; 〇D is the inactivation The optical density of the liquid at the ultraviolet wavelength of the microorganisms (generally in the range of 250 to 280 microns); K is a constant derived from experiments; and tube diameter is the inner diameter of the container in the irradiation area, expressed in cms. 10 g 1. Killing radon or 10 g 1 0 reducing radon (L R V) is here a measure of the efficiency of a method for killing or inactivating microorganisms, such as irradiating a sample containing the microorganism. For example, if 99.0% of all microorganisms in a particular liquid are killed or inactivated, this is equivalent to log 1Q 102 or 2 log 1 (3 kills tadpole or LRV; and others. One can The accepted efficiency is usually found to be 4 to 6 1 0 g! 〇 killing pupae, that is, when 99.9 to 99.9% of all microorganisms in the sample are killed / inactivated. Kill The rate or degree of microorganisms, 'is usually determined in a microbiological analysis test by comparing the initial or initial and final titres of the microorganisms in the liquid (by measuring the maximum number of microorganisms that can be detected exactly Therefore, in one aspect of the present invention, there is provided a device suitable for ultraviolet irradiation of a biological liquid containing a desired component and contaminated microorganisms. The device includes a longitudinally extending container having A wall mechanism of an ultraviolet penetrating substance placed in the irradiation area in close proximity to an ultraviolet radiation source, and having an inlet and an outlet, and a channel mechanism, which are formed and installed to define an extension with almost no substantial discontinuity 10 This paper size applies to China National Standard (CNS) A4 specification (21〇X 297 public love) -------- Order -------- Line—Win (Please read the notes on the back before filling (This page) 474828 A7 B7 V. Description of the invention (?) Flow path to avoid the substantially disturbed phenomenon of liquid flowing through its edges when using the device, and the irradiation area with a wall mechanism adjacent to the ultraviolet transmission, In order to receive ultraviolet radiation from the ultraviolet radiation source when the device is in use, the channel mechanism has a stable flow mixing device having a plurality of mixer members to repeatedly subject the liquid flow to ~ including separation when using the device. And remixing liquid flow mixing operation, the stable flow mixing device will extend along the flow path in at least the irradiation area, the trough device has an inner diameter of at least 4 ha, and the device includes a liquid flow replenishing mechanism 'its When the device is used, it is formed and installed to allow liquid to pass through the container so that the liquid stream is subjected to at least 20 such mixing operations, with an amount not less than the maximum required for effective mixing. The minimum flow velocity of the liquid retention time (in the irradiation area) is performed as shown in Fig. 10. The retention time obtained by killing the gadolinium and above the minimum flow velocity is shown in the maintenance of a substantially linear relationship. A liquid flow rate not exceeding the maximum liquid flow rate corresponding to the minimum residence time required to effectively inactivate the contaminated microorganisms in the irradiated area is performed by proposing a desired 10 g of the microorganisms to kill plutonium, ( It is preferably not less than 4 1 ◦ g of the microorganism, which is generally required for killing tadpoles, generally not less than 1 second, for example, not less than 10 seconds), and not more than the desired component undergoes significant decomposition. At that time, it is preferred that no more than 10% of the desired component be aggregated (the desired is not more than 1%) and / or that the desired component has lost 20% of its biological activity, in which the photos 11 ( (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs

nn II · nn · 1 n I II ϋ ϋ ϋ n I n ϋ n ml I This paper size is applicable to the Chinese national standard iT (CNS) A4 specification (210 X 297 public meals ^ " 474828 A7 B7 V. Description of the invention (/ .) The minimum residence time in the irradiation area is defined according to the relationship shown below: l〇glQ kills 値 X flux (Flux) X residence time / 〇DX tube diameter where the flux refers to the occurrence in the area containing the irradiation The amount of ultraviolet radiation on the channel of the liquid flow is expressed in mW cm —2; OD refers to the liquid in the region of the ultraviolet wavelength where the virus inactivation occurs (generally in the range of 250 to 280 microns). Optical density; κ is a constant derived from experiments; and tube diameter is the inner diameter of the container in the irradiation area, expressed in cms. Wherein when the device is used, substantially all of the liquid can be exposed to a similar degree of inactivation of ultraviolet radiation to the microorganisms And to reduce the damage to the desired liquid component to a minimum. In another aspect of the present invention, a method for processing a biological liquid using the device of the present invention is provided. The biological liquid has a range from 1 to 2000. Duo 値 之(For the avoidance of doubt, unless otherwise specified, all 0 D is a path length of 1 cm to 1 cm). Therefore, it is possible to effectively inactivate biological liquids by the present invention. Microorganisms with high optical density to minimize damage to the desired components of the liquid without the need for additives or other special measurements to achieve microbial inactivation and / or protection of the desired components. However, It will be found that if for any reason it is necessary to include in the device or method of the invention the measurement of the additives and / or the lifetime in the liquid to be treated, this can be done without departing from the scope of the invention 12 This paper size applies to China National Standard (CNS) A4 (210 X 297 public love) ------------ (Please read the precautions on the back before filling this page) Ministry of Economy Printed by the Intellectual Property Bureau Staff Consumer Cooperative

474828 A7 B7 5. Description of the Invention (II) (Please read the notes on the back before filling this page) Protective additives can also be used to reduce damage, such as in the case of agglutination and / or loss of biological activity. Many protective additives are known in the art, including in particular vitamin E, described in W 095/20961 for protecting cells from damage; ascorbate, which protects plasma components from loss of functional activity, as described in WO Agglutination factors in 9 5/3 2 7 3 2; and so-called "quenchers" of free radical groups and / or oxygen-active ingredients such as rutin, quercetin, and other flavonoids ), And other stabilizers such as sugars, such as mannose, and amino acids, to reduce the loss of functional activity of blood components and / or protect against cellular damage, as described in WO 94/28120. Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A special advantage of the present invention is that it can be combined with other different methods to stabilize liquids and inactivate microorganisms easily or slightly when used before or after or at the same time. Various methods are known to some extent in this technology, and specifically include the conventional wet heat treatment or autoclaving, which involves incubating the liquid at an elevated temperature for a specific period of time, such as generally used for albumin, at 60 ° C 10 hours, with or without stabilizer treatment; dry heat treatment, which involves incubating freeze-dried liquid ingredients at an elevated temperature for a specific period of time, such as commonly used for factors such as Factor VIII, 60 to 100 10 to 72 hours at ° C; ultrafiltration; and solvent reagent treatment, in which the liquid system and a solvent reagent system such as 1% tris (n-butyl) phosphate (τ NBP) and 1% Triton X —] _ 〇 〇 or Tween 80 is closely premixed and incubated together for a certain period of time, such as 4 hours at 30 ° C, followed by removal of the solvent reagent system by hydrophobic chromatography in a conventional manner. The details of the processing of solvent reagents are 13 The paper size is in accordance with the Chinese National Standard (CNS) A4 (210 X 297 mm) 474828 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 5. Description of the invention (d) described in W 〇94 / 28120; and various U.S. patent cases, including in particular, case numbers 4,946'648, 4,481,189 and 4,540,573. One of the characteristics of the solvent reagent treatment is that it can significantly increase the OD 値 of the liquid which can be treated, and in this regard, the method of the present invention has the ability to achieve effective virus inactivation in a liquid with a relatively high 0 D 値This is a special advantage. Therefore, in a preferred aspect of the present invention, the ultraviolet irradiation treatment of the present invention is used in combination with a solvent reagent treatment. With regard to the foregoing, it may be noted that different types of viruses have different sensitivities to multiple different treatments' and that it is often necessary to use a combination of different treatments to ensure inactivation of all the different viruses present. A particular advantage of the irradiation treatment of the present invention is that 'a specific type of virus resistant to other easy-to-use treatments such as c P V (canine parvovirus) is more or less highly sensitive to irradiation treatment. Therefore, 'in a preferred form of the present invention for sterilizing biological liquids', the apparatus or method for inactivating microorganisms according to the present invention for ultraviolet inactivation is used together with at least one other microorganism inactivation procedure. According to the present invention, the liquid flow system is subjected to a very thorough mixing, which exceeds the level of liquid homogenization required for the application of the conventional stable flow mixing mechanism to ensure that all parts of the liquid are introduced into the vicinity of the ultraviolet penetrating wall mechanism. A substantially equal residence time in a small irradiation area, whereby all parts of the liquid can accept a substantially equal dose of UV radiation sufficient to achieve the required 10 g of killing plutonium, although there is almost no desire Decomposition of liquid components. Number of flow mixing operations to which the liquid flow is subjected. 14 This paper is sized for China National Standard (CNS) A4 (210 X 297 mm). • ------------ i — (Please read the back first (Please note this page before filling out this page) I · Line · 474828

It will depend on, for example, the factors of the appearance and efficiency of each brain-combining component. 5. Description of the Invention (G), and the liquid flowing through the channel is warm. The secondary flow surface has a steady flow mixing surface with j_Q mixer components. 2 χ i Q = 2 Q hybrid jobs will be provided. It is better to record the greens for the rewards, so that they have to be single-passed to avoid any possible contamination and / or incomplete handling problems. These questions come from the partial_liquid return to the non-facet towel. Its mixing, although it will be understood that multiple passes can be achieved in a way that avoids this danger, for example by using different containers to hold the liquid before subsequent passage. However, 'a multiple-pass system has an advantage, such as reducing the required size and capacity of the irradiating device and providing increased plasticity of operation, which only passes through changes in the number of irradiated areas. More detailed and detailed ^ will understand that the number of mixing operations required will depend on the portion of the channel volume (more precisely, the volume of liquid flow therein) occupied by the irradiation area, which is in the thinner and shallower irradiation area Representing a smaller part of the situation, and therefore requires a higher degree of mixing. This successively depends on the optical density (0 D) of the liquid being processed under the ultraviolet irradiation frequency used, the power and intensity of the ultraviolet irradiation source used, the diameter of the channel, and the stable flow mixing mechanism used. Depending on the channel volume. So, for example, 4'5% HSA has a depth level of 0 · 4 mm relative to the irradiation area of 0 D 2 5 4 値 2 4 .5, with an inner tube diameter of 6 mm and a steady flow mixing The mechanism occupies 50% of the channel volume, and it may alternately require at least 20 mixing operations relative to about 50% of the liquid flow volume, to ensure that the residence time of 10g 1Q killing radon is reached in the irradiation area. With a larger diameter tube, the same depth of the irradiation area (opposite to 15 paper sizes applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm)% (Please read the precautions on the back before filling in this page)

Order --------- line J Printed tube ID (mm) of tube ID (mm) occupied by liquid ° / «tube volume 6 50 8.5 69 13 71 18 74 .... 24 _80 _____ ^ Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 474828 _____B7____ V. Description of the invention (~) The same liquid 0D 値) can be compared to a relatively small part of the channel volume, and therefore it is expected that a larger number of mixing Tasks and hybrid components, although as discussed in this other section, generally use a minimum number higher than hybrid components so that this particular consideration can be considered automatically and normally. It must be noted that during operation, the portion of the tube volume occupied by the stable mixer and the stable mixer of the preferred use type according to the present invention will decrease as the inner diameter (ID) of the tube increases so that the portion occupied by the liquid increase. A typical system is as follows: ___ When a single pass is used, the steady-flow mixing mechanism should have at least 20, preferably at least 30 mixer components, and at least 40 ', preferably at least 50 mixer components. Advantageously, although a significantly higher number of mixer components can be used, such as at least 100 and possibly up to 300 or more mixer components, a particularly high number of mixer components is generally Poor to avoid creating excessive back pressure in the flow path, although it will be understood that a more robustly formed device can be used to construct it's intended to operate at higher pressures. If required, a holding container can also be provided around the container through which the treated liquid passes. At least in the irradiated area, the container should also have a wall mechanism that is substantially UV-transparent. 16 ^ The paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm). I nnnnn 1 n I nn I ϋ _1 1 3. 1 ϋ n I n ϋ n II n I 1 n ϋ nnn > _1 II nnn I. ^ 1 n. (Please read the precautions on the back before filling out this page) 474828 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs System A7 B7 V. Description of the invention (/ 5), such as those made of quartz. As noted above, the degree of virus inactivation in a specific liquid in a specific device is proportional to the residence time in the irradiation area. However, the residence time is the flow rate and the effective length of the irradiation area (that is, relative to Any complex number of the actual length of the illuminated area passed multiple times). As for the minimum flow rate required for effective mixing, it will be understood that there will be a continuous need for the minimum effective length of the illuminated area to provide the residence time required at the used flow rate. (This minimum effective length does depend on various other factors that determine the residence time, including container diameter, 0 D 、 of the treated liquid, and the susceptibility of microorganisms to inactivation, which is specified in the constant κ. Therefore, in In practice, it is desirable to provide treatments, for example, liquids with different OD 値 ranges and / or containing different susceptible microorganisms, and then, usually, the largest one with the smallest effective length required in each different case is usually selected.) Also with regard to the general requirements of the present invention to minimize the harm to the desired liquid components, the devices and methods of the present invention can generally be designed to be closer to the minimum retention required to achieve the desired level of virus inactivation Time corresponds to the maximum flow velocity for a specific length of the irradiation area, and is operated under the circumstances. In this regard, I have found that the 10 g killing system obtained is substantially proportional to the number of mixer components in the container. When the container is substantially the maximum number of mixer components placed therein, The efficiency of irradiation is optimized. Therefore, in a preferred form of the method and apparatus of the present invention, 'the use of a substantially filled mixer member-at least a container in the irradiation area' has the advantage of maximizing the uniformity of the exposure exposure to a maximum of 17 paper sizes. Applicable to China National Standard (CNS) A4 (210 X 297 mm) -nn In I.-· Ϋ 1 III-ϋ < .1 nt ^ i III n II n > nn ϋ > nn —int ^ in ft I (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 474828 A7 B7 V. Description of the invention (4) Optimize to maximize 1 ◦ g It is desirable to minimize the damage to the liquid components, and to optimize the internal cooling, thereby minimizing thermal damage to the desired liquid components. Generally speaking, we have found that effective mixing can be achieved in a practical and economical manner by using 50 to 500, preferably 80 to 350 mixer components. Regarding minimization of the residence time equivalent to maximizing the flow rate, it will be understood that below the minimum effective irradiation area length, a specific desired residence time may be achieved, which has different combinations of flow rate and irradiation area length, as long as An increased flow rate can be reverse-balanced by increasing the length of the illuminated area, and a reduced flow rate can be reverse-balanced by reducing the length of the illuminated area. In particular, high flow rates are generally undesirable because they require relatively large irradiation area lengths, resulting in increased manufacturing costs, increased space requirements, increased useless volume within the device, and increased requirements for irradiation sources. In general, the 'effective irradiation area length (equivalent to the actual irradiation area length in a single pass system) should generally be selected so that it is a minimum effective irradiation area length of 100 to 1 (^ 00%). It is preferably 150 to 700%, and advantageously a minimum effective irradiation area length of 200 to 500%. In general, we have found that for a container having an inner diameter of about 6 mm, 'a suitable effective The length of the irradiation area is usually from 3 to 600 cm, preferably from 40 to 400 cm, and advantageously from 50 to 300 cm. The appropriate flow rate is usually from 40 to 12 0 0 Ml / min 'is preferably 60 to 600 ml / min, and advantageously 80 to 400 ml / min. When used at an actual irradiation area length at the apex of this range, it will indeed be possible. It is found that not all flow velocity ranges 18 This paper size is applicable to China National Standard (CNS) A4 specification (21〇X 297 public love) 噘 ------- —Order --------- line ' (Please read the notes on the back before filling out this page) 474828 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Invention description (I?) Is practical, for example, the velocity at the top of the range can be related to the excessive back pressure previously mentioned here. With a larger container diameter, the effective irradiation area length is relatively As the advancement of the minimum flow rate requirement increases as described previously, similarly, with larger container diameters, the residence time required for a specific 10 g kill level increases proportionally. So 'for example Say, I have found that for a container with an internal diameter of 18 mm (after shrinking and fixing on the mixer member), a suitable effective irradiation area length is usually 100 to 2 0 0 0 Cm, preferably 120 to 1200 cm, advantageously 150 to 800 cm, a suitable flow rate is usually 400 to 600 ml / min, preferably 500 to 40,000 ml / min Advantageously, it is 600 to 300 ml / min. In addition, it will be understood that not all conceivable combinations within this length and flow rate range are feasible. Regarding the minimum flow rate and container diameter Relationship, I have found that The minimum flow rate expressed in liters / minute is usually proportional to the volume of Rong Cui Li expressed in millimeters, it will be surely understood that the minimum residence time in the irradiation area for effective inactivation will be inactivated as required The specific microorganism's sensitivity and susceptibility to the treatment used ', and the relevant ultraviolet radiation dose required are readily available in this literature. Although specific for a particular microorganism, 10 gi. The absolute dose of ultraviolet radiation can be changed by a factor of 10, but the relative sensitivity of different viruses is constant, and provides a reliable prediction of the desired dose of 10 g of radon killing or exposure time for a particular virus, such as 19 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) • I n 1 ϋ nnnl ^ i 11 na— ·· I. ^ 1 n δ, _ · 1 nn I —ma- I n (Please read the precautions on the back before filling this page) 474828 The amount of printed preparations consumed by cooperatives of employees of the Intellectual Property Bureau of the Ministry of Economic Affairs (τη .1 / cm2 1.5 3.0 12.0 15.5 11.0 12.0 11.0 5.8 3.4 3.1 11.0 12.0 10.0 15.4 7.8 240.0 A7 B7 V. Description of the invention (π) Based on "Virus inactivation of plasma products" (ed. Morgenthaler JJ). Curr. Stud. Hematol. Transfus. Basel, Karger 56 pp. 70 -82 is shown in the table below under "inactivation of viruses by ultraviolet light" by Kallenbach NR et al. (1989). Table 1 UVC irradiation dose required for killing tadpoles by og (24 5 nm) virus adenovirus 3 fl lysosomal cW virus Coxsackie virus A9 Coxsackie virus B1 Ico ( Echovirus 1 Echo virus 11 Hepatitis B virus Infectious hepatitis virus Influenza virus Poliomyelitis virus Polio virus 1 Polio virus 2 Polio virus 3 Respiratory and intestinal filtering virus (reovirus) 1 An example of rotavirus SA11 tobacco mosaic virus. See also Marx G. et al. (1996) "Protecting fibrinogen to protect against fibrinogen during UVC irradiation (prOtecting 20) Paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ------------- 暾 ------- —Order --------- Line 丨 j (please read the notes on the back before filling this page) 474828 Employees' Co-operation of Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (,?) Fibrinogen with rutin during UVC irradiation for viral inactivation) '' Photochemistry and Photobiology 63 (4) 541-546; and Connacher J. (1986) "Use The use of UV light for water disinfection '' in The Brewer (May Issue) 0 As shown above, the required residence time will also depend on the special 10 g kill required for the safe use of the treated liquid The extent of death will depend on the microorganisms involved and the degree of microbial contamination. In practice, for microorganisms such as Η I V, B and C hepatitis viruses and small DNA viruses, it is generally required to provide at least 4 10 g :. Retention time for killing radon 〇 Regarding the maximum residence time in the irradiation area that substantially avoids the apparent decomposition of the desired liquid component, it will be understood that this depends on the susceptibility of the component to decomposition and is acceptable in any particular situation Depending on the degree of decomposition. In the case of blood components such as albumin and immunoglobulin, the decomposition effect-mainly occurs in the agglomerated form of albumin molecules, because of the formation of neoantigen, this is very undesired, and other blood The breakdown of ingredients such as blood coagulation factors such as factor VIII, factor IX, and fibrinogen mainly occurs in the form of loss of biological function. Other forms of damage that can be mentioned in this connection include the formation of protein ketone oxidation products . It will be understood that although the general residence time is chosen as close to the desired 10 g 1 (3 as the minimum required to kill 値, in order to reduce the possible damage to the desired ingredients to the minimum. It will also be understood. The role of split boat is not only due to ultraviolet rays -------- order --------- line 丨 '(Please read the precautions on the back before filling this page) 474828

Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the Invention () Effects of Exposure 'is also due to excessive heating that may be caused by being close to the source of UV radiation. This is a particular advantage of the present invention, although it uses a reasonably fast liquid flow and a basic channel diameter that is significantly larger than previously known thin-channel UV irradiation systems (typically 1 mm thick), which provides a A liquid-equivalent entity, any thermal energy absorbed through the entity is rapidly dispersed by very thorough mixing, and has the effect of heating the liquid in whole or in part. It is a method that can be substantially avoided without any additional liquid cooling. Ground, at least some cooled, conventionally assisted gas flow cooling is provided to the source of ultraviolet radiation to help limit the temperature of the tube wall and thus the heat transfer from it to the container. Preferably, the present invention uses a channel diameter of at least 4 mm, advantageously at least 6 mm, and desirably at least 10 mm. Another obvious benefit of using such larger channel diameters is that they facilitate the installation of sources that are effective enough for ultraviolet radiation. Generally, such sources exist in the form of extended low-pressure discharge tubes, which have A diameter of 25 or 35 meters, although higher intensity sources such as medium and high voltage discharge tubes can basically be used. Although the latter is prone to the disadvantages of relatively high experimental temperatures that require the discharge tube to be substantially cooled, the irradiation source tube system is preferably used in a circular array, so that the effective transmission of ultraviolet radiation to the circular irradiation area in the channel is optimal. Into. With very small channel diameters, it becomes impossible to place the light source tubes in a suitable geometric arrangement. It will be unexpectedly found that the actual ultraviolet irradiation flux received by the irradiation area in the channel will have a complicated relationship with the flux emitted from the irradiation source tube. This is particularly due to the optical effect of the channel wall and the illumination source tube and the ring. Due to the number of complicated geometrical relationships between the irradiated areas, the paper size of the table is applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) IIH ϋ n 1 · n · ϋ II-. N I 1 ·· inn I ! n II n I ^ innnnnn I nnn II n · (Please read the notes on the back before filling out this page) Employees of the Intellectual Property Office of the Ministry of Economic Affairs ·; FREE · 474828 B7____ 5. Description of the invention (correction). So far, although the “flux” part of the equation that defines the relationship between the killing and retention time of L og 1 () will remain substantially stable for a particular device configuration, and the main variables such as flow rate, tube The diameter and OD can be easily measured, so the correct part of the flux need not be known. In addition, as discussed further below, any temporary change in flux can be easily monitored by chemiluminescence measurement. . The container may be formed from one or more biologically compatible / acceptable substances such as plastic, biologically deactivated metal or metal alloy, or glass. Preferably, the container is formed of plastic such as PT F E, P MMA, P MA, PE, FEP, PVDF, chlorinated polymer or pyC. Generally speaking, the ultraviolet-transparent container wall mechanism is transparent to electromagnetic radiation with a wavelength in the range of 200 to 400 nm. Preferably, the container is at a wavelength in the range of 220 to 280 nm. Transparent, although UV transmission is optimal at a wavelength of 25 4 nm. The UV-transmitting wall of this device may be made of an inorganic substance such as glass containing oxidized sand, preferably, glass such as those sold under the trade names of Spectrosii and Vitreosil. Alternatively, the wall mechanism may be produced from plastics such as organic polymers, copolymers, and the like such as, but not limited to, cellulose

Formed from PTFE, FEP, P V C, and PE. In general, for a typical wall thickness (usually on the order of 1 mm to 0.5 mm), these materials have a range of 5 to ^-\ λ λ ✓ rr. Ar * A * rart Γ Λγ * ι f 'stf /' 'ft _LrL. ,, ------------- Φ (Please read the notes on the back before filling this page) Order --------- Line-' 474828 A7 B7 V. Description of the invention (> >)% of UV transmission to choose from. In the case of FEP, it has been found that a wall thickness of 150 microns with about 75% U V28 () transmission is convenient. Preferably, the stable-flow mixing mechanism is a generator type of the interface surface, whereby the liquid will pass through the mixing member, which divides the liquid at the inlet of the device into a plurality of substreams, and then redirects and recombines them. This process is repeated on other components until a desired degree of mixing is reached. Advantageously, a stable mixing mechanism is used in the form of an elongated threaded element with spaced-apart mixing members in opposite directions. This type of stable flow mixer is known and has been used for many years. For the purpose, such as the manufacture of food and chemical products, and are commercially available, in particular, they can be obtained by Chemineer Company of North Andover, MA, USA under the KENICS KM brand name and Liquid Control Co., Ltd. of Wellingborough, England under POSIMIXER, and because The combination of several different mixing effects provides very violent mixing, including repeating the flow division of previously separated flows, thereby obtaining the geometric series of flow division, which is based on the formula D = 2 n, Where D is the number of flow divisions and η is the number of mixer components; flow reversal, whereby the rotation direction of each mixer component around the mixer's longitudinal axis is reversed (clockwise-counterclockwise-clockwise) Clocks, etc.); vertical mixing due to the center of each separate flow on the mixer member of the device as the liquid approaches the device The flow reversal and flow inversion that occur at this time are caused by the radial driving outward when encountering the edge of a new mixer; and the axial differentiation (equivalent to the establishment of an axial flow distribution map) inhibition. In this regard, what will be understood is what is specifically intended for a single circulation package 24 -------------% (Please read the note on the back? Matters before filling out this page) tr- -------- Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economics-II n ϋ nnnnnnn I nnnn · This paper size applies to China National Standard (CNS) A4 (210 x 297 mm) 474828 Wisdom of the Ministry of Economic Affairs Printed by the Consumer Bureau of the Property Bureau A7 B7 V. Description of the invention (is) The stable mixer should be in the form of providing a liquid flow, in which there is no obvious difference in flow rate when passing through the diameter of the channel, so that There is no significant change in residence time for different parts of the liquid. Among them, effective substantial radial mixing with no obvious longitudinal or axial mixing is known. This type of liquid flow system is known as "plug flow", and the above-mentioned spiral type stable mixer system is particularly effective for This type of liquid flow is provided. The stable mixer member can be made from a variety of substances that are substantially inert and resistant to damage. In general, the substance should be non-toxic and resistant to decomposition caused by ultraviolet radiation, treated liquids, and any liquids / treatment procedures required for cleaning purposes. Suitable materials include inert metals such as non-brominated steel and plastic materials that are resistant. P VDF (polyvinylidene fluoride) is a particularly suitable plastic material that is highly resistant to ultraviolet radiation. It will also be appreciated that the special form of the above-mentioned stabilized mixer member may provide additional 4 & places such as more local flow rates and / or more efficient mixing, and in this regard, patented TAH may also be mentioned Apple's core cross-section helical mixing element from Industries' stable mixer. It will be appreciated that, especially at higher flow rates, how much significant axial force will be applied to the stable mixer members by the liquid flow, so that generally what these mixer members want is guaranteed to be free of the shaft To the displacement. In the case of glass tube channels, this can be easily achieved by providing radial inwardly extending protrusions as axial stops. In terms of the plastic pipe channel, the pipe can be easily contracted around the mixer member by heat treatment to reduce the inner diameter of the tube, thereby tightly making the outer longitudinal direction of the mixer member 25. This paper size is applicable to China Standard (CNS) A4 specification (210 X 297 mm) ------------ Business -------- Order (Please read the precautions on the back before filling this page)

474828 A7 B7 V. Description of the invention (β) The outer space which is close to and axially separates the mixer components will protrude longitudinally inward to a greater or lesser extent. The liquid flow supply mechanism may be located upstream of the device inlet in a D-cylinder manner, or the liquid may be supplied into the device by gravity feeding. Preferably, the liquid supply mechanism is equipped with a control mechanism capable of adjusting the flow rate to adjust The flow rate of the liquid to a few milliseconds provides any desired residence time within the range previously defined herein. Preferably, for a blood-based liquid, the total residence time in the 'irradiated area is 1 to 100 seconds', and it is desired to be 2 to 16 seconds, and advantageously 8 to 14 seconds. In another aspect, the invention provides a method for irradiating a liquid with ultraviolet light, the method comprising: a) providing a device of the invention; and b) passing a liquid through the device and irradiating the liquid with ultraviolet light in the device; and c) The liquid system passes through the device at a flow rate so that the residence time of the liquid in the irradiated area does not exceed 16 seconds, and preferably does not exceed 8 seconds. 0 It will be understood that it is particularly important to run through -flow) processing program, the stability of the radiation dose received by the liquid through the device can be monitored to at least to a certain degree to obtain some guarantees that the liquid has indeed been safely processed, for example, to ensure that the ultraviolet radiation source is not partially Its outflow is reduced, and thus the flux received in the illuminated area is not necessarily apparent from visual inspection. 26 This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the notes on the back before filling this page). Γ Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs and Consumer Cooperatives. 474828 A7 B7 5. DISCLOSURE OF THE INVENTION (π) We have discovered that ultraviolet radiation from u VC and other commercially available ultraviolet radiation lamps can be used to induce a quantitative chemical reaction, and thus the total exposure received over a period of time can be measured. Therefore, according to another aspect of the present invention, there is provided a method for monitoring ultraviolet radiation received by a liquid flowing through an irradiation area of an ultraviolet irradiation device, which includes the step of providing an actinometeric solution in When irradiated with a specific dose of ultraviolet light, the solution undergoes a substantially quantitative chemical reaction as shown by a change in absorption at a predetermined wavelength; before and after using a device to irradiate a liquid with ultraviolet light to render the virus inactive, Passing the sample of the actinic line intensity measurement solution through the device; and comparing the change in the absorption of the samples of the actinic line intensity measurement solution. Many different solutions for measuring the intensity of actinic rays can be used in accordance with the present invention. Alkali metals, alkaline earth metals, and ammonium iodide salts are particularly convenient. Iodide will be converted to iodine, and its yellow color can be spectroscopic at 3 5 2 nm. Photometer measurement, in addition, the sensitivity of the iodine solution to the dose of ultraviolet radiation can be controlled by adjusting p H ffii, where a lower p Η provides higher sensitivity. Another suitable solution for determining the intensity of the actinic ray may include aqueous uridine monophosphate (UM P), which is converted to U Μ hydrate by UV irradiation (Marx et al, 1996, Photochemistry and Photobiology, 63. 541-546). Although the most effective and efficient killing of viruses is usually obtained by irradiating UV rays at relatively short wavelengths, such as UV C (which has a wavelength of about 254 nm), a variety of sources can be used which provide a number of different wavelengths, of which Some are outside the ultraviolet spectrum and within the visible spectrum. The limitation of using conventional UVC sources is that they have a relatively low energy. 27 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page). Γ Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 474828 A7 V. Description of the invention (Therefore, it is intended to use other sources of higher energy irradiation, such as cylinder-pressure steam lamps and gas-air interrogation lamps (such as High-energy chirps and the like cannot be used continuously and must be quickly vibrated or closed | communicated to avoid damage to the source, etc.), which provide irradiation of UVA and UVB at longer wavelengths and / or include white light and / or Illumination of light in other visible spectrums. Now, the present invention will be further explained in particular with the following examples and attached drawings. Among them: FIG. 1 is a main flowchart of the first device of the present invention; FIG. 2 is 1 is a cross section of the irradiated part of the device of FIG. 1; FIG. 3 is a schematic flowchart of another device of the present invention; FIG. 4 is a cross section equivalent to FIG. 2 of the device of FIG. 3; live The flow chart for the LRV cells; FIG. 6 is based on inactivating the phage L R V of a graph of retention time;

It is a part of the device of FIG. 8; FIG. 7 is a diagram showing the liquid OD of the mixing effect; a close up view;

Printed in detail above is a plot printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. Figure 10 is a graph showing the residence time of L RV irradiated by 4.5% human albumin at a minimum flow rate; Figures of the measurement of the intensity of the actinic lines with different residence times; Figures 12 and 13 show the regression procedures used to determine the Reynolds number function index; 28 This paper size applies the Chinese National Standard (CNS) A4 specification (21〇X 297) (Public love) 474828 Α7 Β7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention (r7) Figures 14 and 15 are inactivated by 10 g of phage in human albumin solution. Figure. ^ Fig. 1 shows a device 1 according to the invention, which comprises a tubular container 2 having a first end 3 with an inlet 4 and a second end 5 with an outlet 6. The arrow A indicates the direction of liquid flow into the device during use, and Arrow B indicates the direction of liquid flow leaving the device. The liquid supply mechanism 7 is provided to allow liquid to pass through the tubular container 2 when the device is in use. Generally, the liquid supply mechanism 7 is a pump that can pump liquid through the device at a desired flow rate, such as a peristaltic pump or a gear pump. . In another installation of the present invention (see FIG. 3), liquid can be supplied to the device 1 by installing the liquid reservoir 7 to maintain a degree substantially higher than the inlet 3 and outlet 5 of the device 1. This installation allows the liquid to flow from the receptacle 7 through the tubular container 2 under the influence of gravity to the outlet 5 which is lower than the receptacle 7. The tubular container 2 of the device 1 is in the form of a silicon tube wall mechanism 8. The tubular container is substantially cylindrical and has a length of about 50 cm, an inner diameter of 6 mm, and a wall thickness of about 1 mm. The four angularly distributed C lamps 9 installed in the reflective housing 10 are located close to the container wall mechanism 8 by a distance of about 5 mm in general. In this case, a suitable lamp system is Those on the market are available from Phillips Lighting of Croydon, England, which has a 15 W power temple 'length of about 48.5 cm, a diameter of about 28 mm, and is sold under the name TUV—15 W. Regarding the control of liquid exposure to ultraviolet radiation, the residence time of liquid 16 is used for monitoring. The 29; paper size applies Chinese National Standard (CNS) A4 specification (21〇 × 297 mm) (Please read the note on the back first) Matters need to be filled out on this page). ¾ tSJ. Line. 4/4828 Γ ——--------- V. Description of the invention () (Please read the notes on the back before filling out this page) The liquid is the opposite In any part of the UV-light penetrating wall tubular container 2 between the UVC lamps 9, this refers to the irradiation area, although it will be understood that the actual time at which any part of the liquid is actually irradiated is equivalent to the phase of the wall of the container The residence time in the adjacent irradiated area will be shorter than the residence time in the irradiated area, and the difference will depend on factors such as 0D 値 of the liquid and the diameter of the container, as described above. The stable flow mixer 11 extends along the length of the container 2 and has-a series of 80 mixer members 1 2 with the longitudinal axis placed on it, 40 pairs of spiral members in opposite directions at an angle of 90 ° to each other The offset exists. The mixer device used is a polyamine and has an outer diameter of 6 mm. It has a push-fit in the silicon tube container 2. The mixer device used is commercially available Metermix Systems Ltd of Wellingborough, England under the name, the components 12 in such devices are formed and installed so that the liquid is completely mixed during use, so that different parts of the body of the liquid are successfully led to the In this way, substantially all of the liquid system is exposed to ultraviolet radiation with a similar degree of inactivation of microorganisms within the shallow irradiation area 12 adjacent to the container 2 ^ wall 8 adjacent to the ultraviolet radiation. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. In order to control the flow rate of liquid through the container, the cartridge 7 is equipped with a control mechanism 14 to adjust the pumping rate. Coriolis mass flow type flow meters 15 are provided to monitor the The volume of the liquid, and can be used to provide an entrance into the cartridge controller 14 or only the operator can use, manually adjust the reading number of the controller 14, the liquid 15 is initially placed in the reservoir 17 and Collected in a sterile container 18 after processing. 30 Paper Size Outline + SS Family Group (CNS) A4 Secret (210 X 297 ^ cent) " ---- 2 8 74 4 A7 _____ B7___ V. Description of the Invention (β) Contact with or close to the container wall 8 The amount of liquid is relatively small compared to the total volume of liquid that is present in the tubular container 2 at any given time, because the liquid basically cools itself during UV irradiation, thereby allowing shallow irradiation adjacent to the tube wall The liquid in the zone will exchange most of the heat obtained during the irradiation, which when flowing through a mixer member 12 to the next remix 'flows the liquid in the tube radially into the irradiation zone 1 3, This cooling effect minimizes thermal damage to liquid components during irradiation. If necessary, the temperature rise can be monitored through the temperature probes 19 and 20 at the inlet and outlet 4 and 5 of the container 2. In practice, the temperature rise is generally limited to about 1 to 2 ° C. Although, as noted above, the absolute flux of the irradiated flux (Flux) or flow (Fluence) is not the most important for successful operation of the present invention, we have calculated this flux for the device of FIG. 1 in the following manner. The device has a group of 4 X 2 8 mm outer diameter (.d.) Lamps, which are connected to a 6 mm inner diameter (i.d.) caliber (8 mm outer diameter) silicon tube at a distance of 7 ^ meters from the surface of the tube. The lines are straight. The exit flux of the lamp measured with a calibrated electronic photometer is 11.8 mW / cm 2 at a distance of 7 mm from the tube surface. However, because the tubes are curved, the surfaces are not parallel, so The flux around the tube is not uniform, and the average intensity of the peak 値 of about 85% is calculated from the manufacturer's Polar diagrams. In addition, the flux in the tube is reduced by light absorption, scattering, and reflection on the wall and surface of the tube. The manufacturer's data for the silicon grade used shows that approximately 85% of the flux will be transmitted at 25 4 nm, so the luminous flux on the inner surface of the tube can be calculated as 1 1.8x0.85x0.85 mW / cm2 or as 8 · 5 31 This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling out this page) = 0 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 474828 B7 _____ V. Description of the invention (b) mW / c m2. Similarly, for the device of FIG. 3, it uses a group of 5 x 40 mm outer diameter tubes (τ UV—115W RVHO) around a plastic tube with an inner diameter of 18 mm, which has a distance of 5 from the surface of the tube. A flux of 25 m W / cm 2 measured in millimeters, allowing the light on the tube surface (90%) and the transmission of the p FEP tube (according to the manufacturer's data '75% at 25 4 nm) After non-uniformity, the calculated flux on the inner surface of the tube (piPe) or tube is 2 5 · Ο X 0 · 9 · 0 · 75 = 16 · 9 mW / cm2. Figures 3 and 4 show another device of the invention, some of which are relative to those in the specific embodiments of Figures 1 and 2. In this case, the tubular container 2 is in the form of three 1, 28 meters long tubes 2 1-2 3, each tube having an inner diameter of 20 mm (fixed to the mixer member 1 during heat shrinking) After 2 it is reduced to approximately 18 mm) and wall thickness of 0.15 mm, and is made of FEP (fluorinated ethylene propylene). U-shaped tube connectors 24 are connected to each other in series. In this case, the liquid supply mechanism simply exists as a high-level receptacle 25, which is formed and installed to supply the liquid to be processed under gravity. The UVC source system in this device includes 8 UVC lamps 2 6 One array, 'Each lamp has a power rating of 1 15 W', is also available from Phillips Lighting under the name T UV-115X RVH 0, and has a diameter of 40 mm and a 1.2 mm diameter. Ruler length. The lamps 26 are arranged such that four angularly distributed lamp systems are located around each of the container tubes 2 1 to 2 3 and the processed liquid is collected again in the sterile container 18. Generally speaking, the above-mentioned device can be used to effectively irradiate ultraviolet rays through 32 scales and apply Chinese National Standard (CNS) A4 specifications (210 X 297 cm) —----- I I --------- ------ II ^-— — 11 ---- line (Please read the notes on the back before filling this page) 474828 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs Α7 Β7 V. Description of Invention (Μ) At 60 and 250 liters of liquid, the liquid has a grade of 0 D 2 5 4 2, a container with an internal diameter of 18 mm per hour, which has at least 4 0x1 7 4 1 ogi. Kill the cricket. The effect of the flow rate on the efficiency of the mixer is confirmed in Figures 5 and 6, which shows the flow rate when treated in the same tube as that shown in Figure 1 installed in a 6 mm inner diameter tube. L ogio or L gio reduces the change in L (RV). Figure 5 shows only the change in L R V 値 at a (volume) flow rate. The same experimental result is shown in Fig. 6, but in this case, the flow rate has been converted into a relative residence time for the liquid when it passes through the upstream end to the downstream end of the irradiation length of the tube 2. In the following figure, it can be seen that when there is a stable and substantial increase in LRV 値, accompanied by a decrease in the residence time (equivalent to a lower flow rate) ranging from 2 to 14 seconds, it exceeds 14 seconds (equivalent to 32 ml / (Minute flow rate), the rate of increase of L RV 値 will be significantly reduced, indicating the disintegration of the high-efficiency mixing condition obtained at a flow rate exceeding 32 ml / min. This practical effect is that the damage to the desired component of the liquid is increased The rate system is proportionally higher, which is particularly undesirable (Similar experiments were performed on larger diameter piping systems, and the minimum flow rate for effective mixing was shown, with an internal diameter of about 2 300 ml / min. ; And the inner diameter of 18 is about 1000 ml / min), in general, the minimum flow rate of ideal mixing can be calculated by the following equilibrium formula: flow rate (ml / min) = 1 · 1 8 5 X (Γ) 3 where r is the radius in millimeters. Using this balance type, the following minimum flow rate can be obtained: 33 This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297ϋ) _ (Please read the precautions on the back before filling this page). ¾-· 474828 B7 V. Description of the invention (θ) Consumption cooperation between employees of the Intellectual Property Bureau of the Ministry of Economy Du printed tube diameter (mm) Tube radius (mm) Minimum flow rate (ml / min) 6 3 3 2 12 6 256 18 9 865 24 12 2050 Figure 7 shows the effect of liquid feed OD 値 on LRV 値, using a device generally shown in Figure 1 at a flow rate of 30 ml / min in a 6 mm inner diameter tube. Initially, it can be seen that when no mixer component is provided in the tube, the LRV will drop very sharply, and its 0 D 値 is still in the single picture. If any, it has an OD higher than 5 to 10値 One of the few valid LRVs 値. In contrast, when the tube was filled with mixer components (80 individual components), an L R V (R) ratio of 4 or higher remained at about 0 D 値. (In addition, similar L RV 値 can still be obtained with even higher OD liquids by increasing the residence time, that is, increasing the length of the tube or reducing the flow rate 'as long as this flow rate is not lower than that applied to a vessel of this diameter (A minimum flow rate of about 30 ml / min). Finally, it shows the expected change in LRV of the liquid OD with the prediction according to the present invention, as can be clearly seen from the figure, the expected change in a wide range of liquid OD and the actual experimental results. There is a fairly good agreement between the measured changes. (It will be understood that an LRV well above 7 is very meaningful in practice, because when the microbial titer exceeds the microbial input titre) Such microbiological titers are usually not measurable). The device 3 1 of FIG. 8-9 includes an optical part 3 2 and an electrical part 3 3. The optical part has five vertically mounted boxes 3 4 (see FIG. 9), and each box is composed of one The four lower 34 papers arranged in the center are in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling out this page > .¾ i. .Line. 474828 A7 B7 V. Description of the invention (w) A circular array of pressure mercury discharge lamps 3 7 is composed of a flow pipe 3 5 which is substantially ultraviolet ray transmissive to the process liquid 3 6. The boxes are connected to each other at the top and bottom to obtain a meandering flow path. The lamps used are Phillips TUV-115W RVHO (with a diameter of 35 mm and a length of 1,200 mm). A UV-C power output of about 10 OmW / c m2 is obtained on the surface of the lamp, and about 85% of the power output system is included in the emission line of 25 4 nm. The program flow tube 3 5 series consists of DuPont fluorethane polymer that shrinks when exposed to heat (Holscot FEP wall thickness 0.2 5 mm before shrinking, inner (I.d.) is 22 mm). This tube is 1.2 meters in length loosely fitted with 72 pairs of spiral mixing members 38 (for PVD F MeterMix PtNo 123 — 608), the The components are assembled with a diameter of 20 millimeters, and are continuously assembled in alternating left and right turns. After being heated by a heat gun to about 110 ° C, the plastic tube will shrink to a final inner diameter of 2 0.5 Mm. Individual program flow tubes 3 and 5 are connected to each other using sanitary clamps with a semi-circular curved portion of a stainless steel tube 38 (Memtech stainless steel flange) with an inner diameter of 20 mm (Metron Tech-Fluorowave Ultrapur Fitting G12). -12-FN-1). At the periphery of each program tube area, six 3 mm X 2 0 mm nitrile Viton (TM) synthetic rubber '〇' rings 3 9 are separated at equal intervals along the length of the tube, Use it as a spacer, and ensure the arrangement of each program tube 3 5 length and the surrounding four lights 37. These lights are mounted on the outer stainless steel box 4 2 hinged door group 4 1 35 Paper size applies to China National Standard (CNS) A4 (210 X 297 mm) —— (Please Read the notes on the reverse side and fill out this page.) · Γ Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 2 8 74 4 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 _B7_ V. Description of the invention (outside) 4 0 Provides isolated and opaque enclosures for easy cleaning and maintenance. The electrical connector 4 3 from the lamp 37 is taken out from the optical part 32 through the waterproof end cap 4 4 and into the electrical part 3 3. In addition to the power supply 4 5 of the lamp 37, the electrical part also includes a lamp monitoring mechanism 46 to monitor the performance of individual lamps by continuously measuring the voltage drop and current of the lamp. The output of the lamp is also monitored individually and individually by means of an interference filter (photon diode sensor 4 7 2 5 4 nm). The flow rate of the program liquid is via a gear with a flow rate controller 4 9 ^ 卽 管 ^ ⑽ 犷 pump) 4 8 to control (SSP Rotary Lobe Pump Pt No SR / 2/018 / S5 driven by European Drive IPC 102 / 80B-4AC), the flow rate range is from 0.5 to 5.0 Liters / minute, and the flow is independently measured in a mass flow meter 50 (Hamall-Crone, Coriolis Mass Flow Meter MFM4085 K / F) to ensure that the flow rate set during the entire process is exactly fi maintain. In the typical case of 4.5% albumin, the flow rate is set at 4.2 liters / minute + /-20%, and this flow rate can process 1,000 liters of albumin in about 4 hours, measured by pressure The device 51 continuously monitors the pressure of the feed stream as it exits the drum and the flow meter, and uses pressure sensors 5 2, 5 3 to monitor the temperature of the incoming and outgoing connections. Encapsulated in optics. Atmospheric temperature is also monitored and controlled by a sealed circulating air conditioning unit 54. The program operation is managed and monitored by a program-controllable logic controller 5 5. The controller can directly control with a SCADA (Supervisory Control and Data Acquisition) program equipment. This standard applies to China National Standard (CNS) A4. Specifications (210 χ 297 mm) " " < Please read the notes on the back before filling out this page)%-° Line · 474828 Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention ( β) The system may be connected with a personal computer 56. During the liquid procedure, clean and disinfect the internal flow path with 1 N N a a, and keep the path filled with sterile pyrogen-free water when not in use. Additional features and advantages of the present invention will be found in the following examples of the use of the device of the present invention, which are provided for illustrative purposes. Example 1 A standard HSA 4.5% w / v aqueous solution (〇D254 = 2 4 · 5), which is a standard HSA solution used in daily medicine to restore blood volume after shock, etc. Prepared from the collected plasma and inoculated at 0X 1 74 (infective dose of 108 / ml), the solution was aspirated through a production-scale UV irradiation device (using UVC lamp with the maximum irradiation energy at the wavelength) (generally similar to the device of Figs. 3 and 4 as previously described). The liquid system was flowed at a flow rate of 4 · 2 liters / minute through three consecutively installed FEP tubes with an inner diameter of 18 mm (each of which was 1.28 meters long and contained 80 mixer members). Surrounded by 4 UVC lamps, a calibrated photometer test system was used to measure the intensity of ultraviolet radiation on the surface of the tube, and it was found to be 2 5 m W / c m2. The stability of the degree of irradiation flux was confirmed by chemical actinometry before or after irradiation, which uses aqueous sodium iodide (1% w / v) and is described in Example 5 below. The monitoring of free iodine production (through an increase in absorbance at 35 2 nm) is described. As a result, the installation allowed 1000 litres of HSA 4.5% to be processed within 4 hours, and reached the pair of phages determined by a conventional phage assay. The paper size was in accordance with Chinese National Standard (CNS) A4 specifications. (210 X 297 mm) ------------ Can -------- Order (Please read the notes on the back before filling this page)

474828 A7 B7 V. Description of the invention (M) (Please read the precautions on the back before filling in this page) 10 g of fungus 4.5 kills 値. -In general, the irradiation will cause the albumin dimer portion (as measured by gel filtration method 8) to increase from 5.4% of the original content to 6.1% '8% aggregate content (with gel Ingredients with a molecular weight greater than 2xlO6 Da measured by the method) are not changed after the gel filtration process, "after the liquid is irradiated," and the temperature rise with an initial temperature of 20 ° C is generally limited to about 丨. 0. Example 2-Irradiation of Human Plasma The collected blood (0 D 2 5 4 = 5 5 · 0) inoculated with 0X 1 7 (1 0 8 P fu / ml infectious dose) was sucked through- In a laboratory-scale irradiation device (254 nm), the irradiation device is generally similar to the device of FIGS. 1 and 2. The liquid system passes through a single 6 mm inner diameter silicon tube (48.5 cm long and contains 80 mixer components). The tube system is surrounded by 4 UVC lamps to specifically provide 10 mW on the surface of the tube. / c m2 of ultraviolet radiation. The flow rate is 40 liters / minute (2.4 liters / hour), which provides a residence time of 1 1. · 1 second in the irradiation area of the tube portion of the ultraviolet (lamp), lamp intensity, and radiation system. Measured as described in Example 1. Results Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Generally speaking, the LRVs measured using the procedures described in Example 1 were between 3.6 and 40. After irradiation, the initial temperature was 2 0. < 3 The rise in liquid temperature is 1. 〇, the recovery of plasma components (based on their retained biological activity, as determined by agglutination assay) is as follows: FVIII: C 80-90%, FV 7 5-80% above fibrinogen 7 5 — 8 5%. 38 This paper size applies _ National Standard (CNS) A4 specification (210 X 297 Public Love ^ 474828 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (π) Example 3-Human immunoglobulin Irradiation (1 g G) 1 gG (150 g / l; 0D254 = 20〇) inoculated with 0x174 (10 Pfu / ml) was placed in a cooled container (at 4 ° C) ) And recirculated the device at a flow rate of 100 ml / min as described in Example 2 until a period equal to 24 passes (equivalent to a total retention of 106 seconds in the illuminated area in the tube) Time), lamp intensity and radiation are measured in the manner described in Example 1. Results In general, L RV (as determined in the previous manner) is 4.2 and the aggregate content (molecular weight is greater than 2 xlO6 Da) (as previously described) The measurement) was increased from 4.7% to 5.2%. In functional analysis, the irradiated IgG line showed a 10% to 15% reduction in anti-streptolysin 0 antigen and anti-rubella antibodies 10% reduction in content. Example 4-Sample line of mammalian virus-inactivated human albumin (4.5% concentration) Inoculated with a selected mammalian virus and treated using a device and method similar to those described in Example 2, but performed at a low flow rate of 30 liters / minute, which is provided in the illuminated area of the UVC lamp tube section Retention time of 14 seconds. Viruses are selected depending on their general resistance to heat treatment and / or solvent cleaning. Although as mentioned earlier, different viruses usually have different sensitivities to ultraviolet radiation, but the samples are all Processed under the same conditions: at a flow rate of 30 ml / min. Results The following LRVs obtained by the virus being processed are shown in Table 2: 39 This paper is scaled to the Chinese National Standard (CNS) A4 grid (210 X 297 mm) n — ^ i 1§ i ftn I l ^ i · nnn US —inm J'_ ^ 1 · n if ft—vnnn I an word (please read the notes on the back before filling this page) 474828 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs V. Invention Description (y) Viral genome / type LRV Sindbis single-stranded RNA > 3.2 SLFV (Semliki Forest Virus) single-stranded RNA > 4.3 SV40 (Simian Virus 40) double DNA 4.2 CPV (Canine Parvovirus) single-stranded DNA of respiratory and intestinal filter virus > 6.0 (Reo virus-3) double-stranded RNA 3.6 HSV (herpes simplex virus) double-stranded DNA 2.5 0X174 double-stranded DNA 6.2 from Table 1 (above) and It will be known in Table 2 that the absolute and relative sensitivity of E. coli phage 0X174 can represent internal standards to predict the relative possible killing of all other viruses represented in these tables. Therefore, for example, In Table 1, by comparing the sensitivity of adenovirus 3 with the sensitivity of bacteriophage (E. coli), it can be predicted that for any given set of irradiation conditions, 10 g of killing plutonium of adenovirus will be The bacteria are twice as much, and conversely, the kill of the infectious hepatitis virus is about half that of phages. In the table of the results of Example 4 above, 'can be predicted that under any specific set of irradiation conditions, dogs A 10 g killer of parvovirus will equal or exceed a 10 g killer of phage 0X174, whereas a 1 g killer of sindbis will be about half as fast as 0x174 of the fungus. Therefore, by incorporating the Liaoliao bacterial cell 0X174 into any known product and setting the conditional cutting assay to kill 10 g of plutonium, it is possible to predict the possible 10 g of plutonium of any other virus. We have found that it is possible to reproducibly obtain a consistent 0x174-0 g kill 値 under fixed conditions such as 4.2 + /-Q. 2, so we give a good degree of confidence to the above prediction. 40 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) -----------------! | Order--------- line (Please read the precautions on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 474828 A7 B7 V. Description of the invention (π) Example 5-Determination of the intensity of chemical photochemical lines using 1% sodium iodide W / v in 5mM tris-HC1 pH 7.5) Sodium iodide is pumped through the irradiation device under the same conditions as used for processing the albumin liquid being monitored, with 4.5% of human blood ' In the case of albumin, this method will cause the sodium iodide solution to be pumped through a production-scale device (described earlier) at a flow rate of 4.2 liters / minute, which is equivalent to the volume of the dead volume, And a sample of the irradiated sodium iodide solution (about 300 ml) was collected for spectrophotometric measurement at 35 2 nm (at least 2 hours after irradiation). Before the albumin liquid was irradiated, the device was flushed with saline. After the albumin liquid was irradiated, the actinometer method was repeated in the manner described above. 1 · 0 of 0 D 3 5 2 値 is equivalent to a flow rate of 10 OmJ / cm2. In addition, the iodide light intensity reagent can be changed in sensitivity if necessary to suit the experimental conditions used. Therefore, we routinely use 1% NaI at 50 mM Tris pH 7. Sensitivity can be increased considerably with buffers such as citrate or borate, respectively, by reducing PP to eg 3.0, or it can be considerably reduced by increasing pΗΗ to 9 · 2. The reagent for measuring the intensity of the iodide can be compared in absolute units (m J / c m2) by using potassium ferric oxalate reagent, such as Jagger, J., (Potassium Ferrioxalate Actinometry, In "Introduction to Research in Ultraviolet Photobiology ,, 1967, pages 137-139, Prentice-Hall, New Jersey). This is more conveniently performed in, for example, a small laboratory-grade device, such as Figures i and 41. This paper size applies the Chinese National Standard (CNS ) A4 size (210 X 297 mm)

Hill — — — — — — — I i IIIIII ^ «— — — — — — I— (Please read the precautions on the back before filling out this page) 474828 Printed by the Consumers’ Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (2) The device '2 uses a silicon tube of 6 mm inner diameter with a length of 4 8.5 cm, and is covered with aluminum foil to limit the length of the tube to 2.5' 5 _0, 7 · 5 cm, etc. This line is necessary because the sensitivity of the ferric oxalate reagent is higher than that of iodide at P Η 75. A graph can then be constructed to correlate the optical density of the iodide solution at 35 2 nm with the relative fluence (flux multiplied by the residence time in seconds) in mj / c m2. The flux map for each machine structure can be obtained by dividing the observed flow rate by the residence time (in seconds) of any particles in the illuminated (irradiated) part. Figure 6 (???) illustrates the calibration curve we obtained to convert the iodide A 3 5 2 n m map to the flow rate, which should be independent of the machine but will change with the p Η of the iodide century. The use of the iodide photochemical intensity measurement reagent system described herein has a significant advantage over the iodide reagent. Unlike the uracil nucleoside monophosphate reagent, 'the reagent iodide causes an increase in optical density during re-exposure. And the change of the spectrum is visible to the naked eye, which allows the operator to pay attention and modify the function of the device. This change in color shows that immediate and no titling is needed for offline sampling like the ferric oxalate method 'and that this allows a flow spectrophotometer to be continuously or intermittently automated on-line to measure the intensity of the actinide. Another advantage of this iodide reagent is that it can adjust the sensitivity to suit the exposure dose to be used in this procedure 'which allows a wide range of kinetics, unlike iron oxalate reagent in most practical applications Tends to follow the scale (off_scale). Another advantage of iodide reagents is that they are cheap and easy to prepare and stored in large quantities before use ' and they are convenient for large volumes when calibrated and monitored in the largest scale process equipment in an industrial environment. 42 This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) I1IIIIIII1I —-丨 丨 丨 丨 丨 丨 丨 丨 丨 丨 丨 — — * (Please read the precautions on the back before filling in this Page) 474828 Printed by A7 B7, Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the Invention (called) Examples 6 to 9-Irradiation of Human Albumin The parameters required to kill the 値 relation. The viscosity of the human albumin solution (4.5% and 20% v / V) in this test was measured by a commercially available Synchro-Lectdc viscometer (Brookfield Engineering Laboratories, Stoughton, Mass, USA), which used A cylinder or disc rotates in a liquid and measures the torque that overcomes the viscous resistance to induced motion. This measurement can be accomplished by driving an immersed member (called a spdndle) through a beryllium copper spring to achieve an in-viscosity The degree of damage to the spring indicated by the position of the object in red on the gauge dial is proportional to the viscosity of the liquid along any particular speed and sprindle. It was found that the viscosity of 4.5% Η A was 1.36 cp and the viscosity of 20% HA was 5.0 c ρ 〇 4.5% and the density of 20% human albumin solution were found to be 1010 and 1051 kg at 20 ° C, respectively. / Square meter, which is the density obtained by measuring the weight of a known volume of protein solution at a specific temperature and calculating the weight. Example 6-Determination of the minimum flow rate of 4.5% Η A 4-5% human albumin batches are generally irradiated as described in Example 2 at a series of different flow rates. Each time the measurement was performed, 10 g of killing radon (L R V) was measured and the retention time (seconds) obtained by measuring the flow rate as shown in FIG. 10 was plotted. It also shows the 10 g kill 値 predicted by the general relationship of the present invention, which is measured as the measured 値 (shown below). From these measurements 値, it is known that the residence time exceeding the rank of 10, Experiment 43 This paper size applies to China National Standard (CNS) A4 specification (210 X 297 public love) -------------% ------- • " Order ----- ---- Line (please read the notes on the back before filling this page) 474828 A7 B7 V. The 10 g kill of the invention description (U) will substantially deviate from the predicted 1 g kill rate, and A slight increase in killing plutonium of 10 g was obtained with increasing residence time (relative to reduced flow rate). Taking density, viscosity, and linear flow velocity relative to this residence time into consideration, it was found that the deviation of predicted radon occurred when the number of Reynolds was 50 again. Results-(Ultraviolet irradiation with 4 xl5w UVC lamps with a 6 mm inner diameter 3 6 cm long silica glass tube) (Volume) Flow rate (meters / minute) Number of Log killing Reynolds 5 7 13.1 10 6 26.2 20 5.4 52.4 32 4.8 83.9 45 4.1 118.0 174 2.3 / 456.3 -------------% (Please read the notes on the back before filling this page) Order --------- line & quot Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs using the above-mentioned minimum flow rate measurement, it is possible to predict the minimum flow rate (umin) for other tubes to silence other liquids, which uses the following relationship: Umin-5 0 μ / dp, where μ , D, and p have the same meaning as before. 44 This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 474828 A7. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (») B7 Solution tube ID, minimum flow rate in millimeters, ml / min 4.5% HA 10 33 4.5% HA 13 43 4.5% HA 20 67 20% HA 6 74 20% HA 10 123 20% HA 13 160 20% HA 20 246 Example 7 -Determination of 1% sodium iodide dissolution of p Η 7 using the minimum flow rate for the determination of the intensity of the actinic line In the batch system is generally irradiated as previously described, which is based on silicon tube 194 cm long 6 mm internal diameter manipulation performed with different flow rates. The absorbance of the obtained irradiated solution is plotted against the flow rate in the form of residence time in seconds. As shown in Fig. 11, the absorbance will increase with the residence time (equivalent to the control). Set the exposure time to increase) and increase linearly, up to a retention time of about 60 seconds with a flow rate of about 30 ml / min, which in turn corresponds to the number of Reynolds at a flow rate of about 50. The rate of increase in absorbance decreases substantially with increasing retention time relative to lower flow rates and lower numbers of Reynolds, thereby also exhibiting a reduced mixing efficiency. Example 8-1 Measurement of the liquid property function of the relationship between the 10 g killing radon and the treatment parameters of the liquid irradiation treatment The UV irradiation of the liquid of the OD 値 is based on the depth of ultraviolet penetration into the liquid, and is therefore effective Depending on the proportion of the volume of all the channels in the irradiation area that are exposed to ultraviolet radiation, and depending on the middle of the channel, the main liquid is

This paper size applies to China National Standard (CNS) A4 specifications (210 XI n 1 ^ 1 nnnnnnnnnnn as— aaal nnnn I n I— II n 1 i __— n. (Please read the precautions on the back before filling out this page) 45 474828 A7 B7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention (called) The body's replacement of the liquid in the illuminated area. The latter depends on the mixing device used. This type of stable mixer obtains a highly efficient radial mixing (between the radial interior and the radial exterior of the channel), and this is a function of the Reynolds number of the liquid being mixed, ie / (R e ). Taking this as a consideration, the obtained 10 g killing 値 is determined by the following relationship: 1 ◦ g kill 値 = k / (R e) I (pu) (L / R e) 〇 D · d Where μ is the viscosity of the liquid in cp, p is the density of the liquid in kg / m3, d is the diameter of the liquid channel in mm, Re is the number of liquid Reynolds, and L is effective Channel irradiation length, OD is in mW / c m2 The intensity of the inner wall of the channel is the optical density of the liquid. The above relationship can be arranged as follows: I k / (Re) = 1 og kills 値 · 〇D · d L / R e I (ρ / μ) which can be expressed as: k / (Re) = K Rem. The constants K and exponent m are derived from the 10 g kill 値 measurement 値 and other parameters 回归 (Figure 1 & 2 and Figure 3 & 4). Since stable mixers of the same form (geometry) are used in both devices, the index m of the two devices will remain the same during regression, as shown in Figures 1 2 and 1 In 3, the regression is performed when m is in a range of 0.5 to 0.7, and it is found to be the most suitable. 46 (Please read the note on the back? Matters before filling out this page)% Top 5: Thread paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) 474828 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 ______B7 ____ V. Invention Description (0 is when m has a time of about 0.6. (Note- For less effective blends at low rates equivalent to a number of Reynolds below 50, The obtained measurement is of lower significance). The above-mentioned index m of 0.6 which is obtained by 値 ′ then predicts that the relationship of 〇g killing 値 has the following form: 1 ◦ killing 値 T m (dXll) l_ 〇D · d Re0.4 where K is determined by the sensitivity of the virus species to the inactivation of ultraviolet radiation and the power of the ultraviolet radiation source, and can be determined by some tests performed. (Tm is the ultraviolet transmittance of the tube wall, that is, Tm = k'I, where I has the same definition as before, and k is a constant equivalent to the specific ultraviolet irradiation source and assembly used. Example 9 A human albumin was irradiated with a standard 4.5% w / v ΗA aqueous solution (〇d 254 = 1 2 · 8) inoculated with phage 0X 1 74 (infective dose 108 / ml) in a laboratory-scale device In the two series of experiments, each experiment system includes a range of different flow rates relative to different residence times. The viscosity and density are The measurement was performed in the manner described previously. The 10 g killing system obtained was plotted against the residence time (as shown in Figure 14) and compared to the predicted 10 g kill obtained from the general relationship according to the present invention. Dead line (continuous line) comparison, the predicted 10 g kill line uses the above-mentioned liquid viscosity and density data, Reynolds number function parameters (m = 0.6, K = 0.117), and device parameters (d = 6mm 'L = 36cms, mixer key volume 5 0 47 This paper size applies National Standard (CNS) A4 Specification (210 x 297 mm)-Order --------- Line IAW (Please read the notes on the back before filling this page) 474828 A7 B7 V. Description of the invention (4 )%). From Figure 14 it can be seen that the 10 g kill 値 measurement of both series is criminally and numerically very similar to the predicted 10 g kill 値. It will be understood that the increased residence time It can be obtained by increasing the number of times the liquid passes through the irradiated area without changing the flow velocity, instead of changing the liquid flow velocity and velocity u. In this case, it will be obvious that the number of Reynolds will not change and 10 g kills radon and retention The relationship between time will be linear, as shown in Figure 15, which is based on the experimental results obtained with a 20% w / v human albumin solution in a large-scale device and a 18 mm ID FEP liquid. Comparison of flow tubes. It is intended that the previously described embodiments are not limited to the scope of the invention, and it will be appreciated that different modifications can be made to the previously described without departing from the scope of the invention. A brief description of the symbol of the component -------------. (Please read the notes on the back first (Please fill in this page again) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 1 Device 2 Tubular container 3 First end 4 Inlet 5 Second end 6 Outlet 7 Liquid supply mechanism / reservoir 8 Silicon tube wall mechanism 9 UVC lamp 10 Reflection Shell 11 Stabilized flow mixer 48 This paper size applies to Chinese national standards (CNS> A4 size (210 X 297 mm) 474828 A7 _B7 V. Description of the invention (叼) 12 Mixer component 13 Irradiated area 14 Control mechanism 15 Flow meter 16 Mixer component 17 Reservoir 18 Sterile container 19 Temperature probe 2 0 Temperature probe 2 1 Long tube 2 2 Long tube 2 3 Long tube 2 4 U-shaped tube connector 2 5 High-level receptacle 2 6 UVC lamp --- ----- Order --------- line IAW. (Please read the notes on the back before filling out this page) Printed by the Employee Consumption Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 49

This paper size applies to China National Standard (CNS) A4 (210 X 297 mm T

Claims (1)

474828 (Please read the precautions on the back before writing this page) 1. A device suitable for ultraviolet irradiation of a biological liquid containing the desired ingredients and contaminated microorganisms. The device contains a longitudinally extending container with The wall mechanism of the ultraviolet penetrating substance in the irradiation area, which is very close to the ultraviolet radiation source, and has an inlet and an outlet, and a channel mechanism 'which is formed and installed to define a flow path extending therebetween with almost no substantial discontinuity, in order to To avoid the substantially disturbed phenomenon of liquid flowing through its edges, and the irradiation area having a wall mechanism adjacent to the ultraviolet light penetrating, to receive ultraviolet radiation from the ultraviolet radiation source when the device is used, the channel mechanism has a A stable flow mixing device having a plurality of mixer members to repeatedly separate and remix the liquid flow when the device is in use. The line-shoulder container has an inner diameter of at least 4 mm, and the The device includes a liquid flow replenishing mechanism formed and installed to pass liquid through the container when the device is used So that the liquid stream is subjected to at least 20 such mixing operations, which is performed at a liquid flow rate (within the irradiation area) that is not lower than the minimum flow rate required for effective mixing relative to the maximum liquid residence time, As shown by the maintenance of the substantial close relationship between the actual 10 g kill 値 and the 10 g kill 値 predicted by the relationship shown below, and to obtain the increased residence time of the minimum flow rate described above and The liquid flow rate does not exceed the maximum liquid flow rate corresponding to the minimum residence time required to effectively inactivate the contaminated microorganisms in the irradiated area by killing plutonium by providing a desired 10 g of the microorganisms. It is better to be no less than 4 1 〇1 ^ Paper size common Chinese national standard (CNS> A4 specification (210 X 297 mm) '474828 058899 ABCD VI. Application for patent scope g Those who need to kill radon, general and Say not less than 1 second, for example, not less than 10 seconds), and not more than the time when the desired component is clearly decomposed, preferably not more than 10% of the desired component is aggregated (the desired is not more than 1%) and / or the time when the desired component loses 20% of its biological activity, wherein the minimum residence time in the irradiation area is defined according to the relationship shown below: 1 Ogio kills 値 = KX flux (Flux) X residence time X2 / 〇d X tube diameter where flux refers to the amount of ultraviolet radiation that occurs on the channel containing the liquid flow in the irradiation area near the channel wall, expressed in mW Cm-2; 0D is The optical density of the liquid at the ultraviolet irradiation wavelength (generally in the range of 250 to 280 microns) of the inactivated microorganism; κ is a constant obtained from experiments; the tube diameter is the inner diameter of the container in the irradiation area, Expressed in cms; and Z = u (ρ / μ) / ί1 em where U is the liquid flow rate in cm / s, p is the liquid density in kg / m3, and μ is in cp Unit of liquid viscosity, Re is the Reynolds number of the liquid, this 値 is defined by the formula Re = d U ρ / μ, where d, u, p and μ have the same definitions as above, and m is for this A characteristic of a stable hybrid system, which is determined experimentally, by which the use of the device is essentially Some liquids can be exposed to ultraviolet radiation with a similar degree of microbial inactivation, while at the same time reducing the damage to the desired components of the liquid to a minimum. _ 2 _ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) (Please read the precautions on the back before filling this page),-° line 474828 A8 B8 C8 D8 — ___ .--- -.-. I .......... VI. Patent Application Fan Park (Please read the notes on the back before writing this page) 2. According to the device of the patent application Fan No. 1, the device Formed and installed at a flow rate that is not less than the minimum flow rate equivalent to the maximum liquid residence time required for effective mixing in the illuminated area, such as 10 g killing radon and retention at the minimum flow rate obtained above A maintenance of a substantially linear relationship between time is shown 'and a (minimum) desired 10 g killing effect by passing a liquid stream through the irradiation area' to provide a (minimum) residence time in the irradiation area, which The residence time is defined according to the following relationship: 1 ogio kills 値 = Kx flux X residence time / 〇 [) x tube diameter, where flux refers to the amount of ultraviolet radiation that occurs on the channel containing the liquid flow in the irradiation area. mW cm〃 said; 〇D is essentially The optical density of the liquid in the ultraviolet wavelength region where the inactivation occurs (generally in the range of 250 to 280 microns); K is a constant obtained from experiments; and tube diameter is the inner diameter of the container in the irradiation area , Expressed in cms. 3. The device according to item 1 of the scope of patent application, wherein the stable flow mixing mechanism has 50 to 500 mixer members. 4. The device according to any one of claims 1 to 3, wherein the container has an inner diameter of at least 6 mm. 5. The device according to item 4 of the scope of patent application, wherein the container has an inner diameter of at least 10 mm. 6. The device according to any one of claims 1 to 3 of the patent application scope, wherein the container wall mechanism is substantially transparent to ultraviolet rays in a wavelength range of 220 to 280 nm. _ 3 types of this paper, it ’s a kind of family. (CNS) A4_ ^ 21Gx297i'i) ^-474828 D8 VI. Application scope of patent 7. Device according to any one of the scope of patent applications 1 to 3, where The effective irradiation area length (equivalent to the actual irradiation area length in a single-phase system) is 100 to 1000% of the minimum effective irradiation area length. 8 The device according to item 7 of the scope of patent application, wherein the effective irradiation area length is a minimum effective irradiation area length of 150 to 700%. 9. The device according to any one of claims 1 to 3, wherein the liquid flow supply mechanism includes a drum mechanism. 10. The device according to any one of claims 1 to 3 of the scope of patent application, wherein the liquid flow supply mechanism is equipped with a control mechanism capable of adjusting the flow rate, which can be adjusted to provide a desired when using the device. Liquid flow rate 0 1 1 The device according to any one of claims 1 to 3, wherein the liquid flow supply mechanism is formed and installed to provide a liquid residence time of 1 to 100 seconds when the device is used. 12. The device according to item 11 of the scope of patent application, wherein the liquid residence time is 2 to 16 seconds. 1 3. A method for irradiating a liquid with ultraviolet rays, the method comprising: a) providing a device according to item 1 of the scope of patent application; and b) passing the liquid through the device and irradiating the ultraviolet rays in the device with ultraviolet rays liquid. 14. The method according to item 13 of the scope of patent application, wherein the liquid system passes through the device at a flow rate so that the liquid stays in the irradiated area 4 _ This paper size applies the Chinese National Standard (CNS) A4 specification (210x297 mm) Li> (Please read the notes on the back before filling in this page) A8 —--- 08 .... _ VI. Scope of patent application Time is 1 to 100 seconds. 15 · The method according to item 14 of the scope of patent application, wherein the residence time is 2 to 16 seconds. 16. A method according to any one of claims 13 to 15 of the scope of the patent application, which comprises the step of introducing a protective agent into the liquid. 17 · A method for sterilizing a biological liquid, which comprises a method for irradiating ultraviolet rays as described in any one of claims 13 to 15 and a method for inactivating at least one other microorganism. 18. The method according to item 17 of the scope of patent application, wherein the method for inactivating at least one other microorganism is selected from the group consisting of heat treatment and reagent treatment. Nineteen types of monitoring the ultraviolet light received by the liquid flowing through the irradiation area of the ultraviolet irradiation device include providing a solution for measuring the intensity of an actinic line. When a specific dose of ultraviolet light is irradiated, the solution passes through a substantially Quantitative chemical reaction 'The reaction shows a change in the absorbance of a predetermined wavelength; before or after using the device to irradiate the liquid with ultraviolet rays to inactivate the virus therein, a sample of the photochemical line intensity measurement solution is passed through the device. And comparing the intensity of the actinic line to determine the change in absorbance in the solution sample. 20 · The method according to item 19 of the scope of the patent application, wherein the solution for measuring the intensity of the actinic ray is selected from the group consisting of alkali metals, alkaline earth metals, and stilbene salts, and aqueous uridine monophosphate. 2 1. The method according to item 20 of the scope of patent application, wherein the solution for measuring the intensity of the actinic ray includes an aqueous sodium iodide solution. 2 2 · According to any of the items 19 to 21 of the scope of patent application-item 5 (please read the precautions on the back before filling out this page) 1ΤΪ ^ The paper size is applicable to China National Standard (CNS) A4 specifications < 210 X 297 mm) 474828 A8 B8 C8 _ D8 6. Method for applying for patent scope 'wherein the photo-stoichiometric solution contains a pΗ buffer solution. 2 3 · A method for irradiating a biological liquid containing a desired component and contaminating microorganisms, the method comprising the following steps: a) providing a device comprising a longitudinally extending container having an ultraviolet radiation in close proximity to the irradiation area The wall mechanism of the source's ultraviolet penetrating substance 'and has an inlet and outlet and a channel mechanism formed and installed to define a flow path extending therebetween with almost no substantial discontinuity to prevent liquid from flowing through its edges. Substantial scramble phenomenon, and an irradiation area having a wall mechanism adjacent to the ultraviolet penetration to receive ultraviolet irradiation from the ultraviolet irradiation source when the device is used, the channel mechanism has a The spike fixed flow mixing device is used to repeatedly separate and remix the liquid flow when using the device. The container has an inner diameter of at least 4 mm, and the device includes a liquid flow replenishing mechanism. And is arranged to pass liquid through the container when the device is used, b) to pass the liquid through the container A container such that the liquid stream performs at least 20 such mixing operations at a liquid flow rate (within the illuminated area) that is not lower than the minimum flow rate required for effective mixing relative to the maximum liquid residence time Perform 'maintaining a substantial close relationship between the actual 10 g kill 値 and the 10 g kill 値 predicted by the relationship shown below, and to obtain the increased residence time of the minimum flow rate described above and At a liquid flow rate that does not exceed the maximum liquid flow rate corresponding to the minimum residence time required to effectively inactivate the contaminated microorganisms in the irradiated area, it is performed by increasing the national paper standard (CNS) A4 specification 2W X 297 male cage) 1 ~ '(Please read the precautions on the back before filling this page) 474828 A8B8C8D8 6. The scope of the patent application is for a desired log killing of the microbe of the microorganism (preferably not less than 4 10 g of the microorganism required to kill the tritium, generally not less than 1 second, For example, not less than 10 seconds), and not more than when the desired component is significantly decomposed, preferably not more than 10% of the desired component is aggregated (the desired is not more than 1%) and / or the When the desired component loses 20% of its biological activity, the minimum residence time in the irradiated area is defined according to the relationship shown below: 1 〇g 1 〇 Kill 値 = KX flux (Flux) X Retention time XZ / 〇DX tube diameter where flux refers to the amount of ultraviolet radiation that occurs in the channel containing the liquid flow in the irradiation area near the channel wall, expressed in mW cm — 2; 0D is the inactivated microorganism The optical density of the liquid at the ultraviolet irradiation wavelength (generally in the range of 250 to 280 microns); K is a constant obtained from experiments; tube diameter is the inner diameter of the container in the irradiation area, expressed in cms; and Z = η (ρ / μ) / K em where U is in cm / s P is the liquid density in kg / m3, μ is the viscosity of the liquid in C p, and Re is the number of Reynolds in the liquid, which is given by the formula R e = d U ρ / μ, where d, U, p, and μ have the same definitions as above, and m is a characteristic of this stable mixing system. 'The system is determined experimentally, thereby making virtually all liquids accessible to A similar degree of inactivation of ultraviolet rays, while reducing the damage to the desired components of the liquid 7 __ ^ Paper size applies ^ National Standard (CNS) A4 specification (210 X 297 public love) (Please read the precautions on the back first Rewrite this page) 474828 A8 B8 C8 D8 The scope of patent application is at least (please read the notes on the back before writing this page) Aw --0 line This paper size applies to Chinese national standards (CNS> A4 specifications < 210 X 297 mm)